Neural stem and progenitor cells and neocortex expansion in development and evolution

Our goal is to elucidate the molecular and cellular mechanisms underlying the evolutionary expansion of the neocortex, specifically the increase in the number of cortical neurons generated during embryonic/fetal development. Ultimately, we aim at identifying the genomic changes that are responsible for the increase in neuron number in the human neocortex as compared to other primates.

Towards this goal, we take the following approaches.

1. We characterize neural stem and progenitor cells (SPCs) that generate neurons in the developing neocortex of a variety of species (mouse, ferret, marmoset, human), and determine their lineage. Using this knowledge, we study the differences across mammals developing a lissencephalic versus gyrencephalic neocortex, in order to obtain insight into neocortex evolution.

2. We investigate specific cell biological features of the various cortical SPCs, including their cell polarity and organization and dynamics of intracellular organelles, in order to obtain clues as to their differential proliferative potential.

3. We study the cell cycle and cell division of cortical SPCs.

4. We explore the role of genes, mutations in which cause microcephaly, and develop novel technology to functionally search for, and test, candidate genes for neocortex expansion.

5. We analyze the transcriptomes of cortical germinal zones and specific SPC subpopulations, in order to identify, and then functionally test, candidate genes for neocortex expansion.

Wieland B. Huttner on "Which Evolutionary Changes in the Genome Led to the Development of the Large-Sized Human Brain?"